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Global support and standardization of regulation for biosimilars approval owes much of its legacy to the World Health Organization (WHO), since the first guidance by the organization on the matter was released in 2009. Since then, and with over a decade of research, the 2022 revision provides opportunities for time and financial savings to pharmaceutical manufacturers aiming to prove similarity of a potential biosimilar product to some reference product, particularly by clarifying that the use of a non-local reference product as a comparator in certain studies is permissible. This declaration has important implications, particularly in the emerging biological markets of the Middle East and North Africa region, where WHO guidelines have been integral to the regulatory framework of over a dozen countries for more than a decade. This article aims to review the impact of this revision on these countries and relevant policies on non-local comparator usage. Since 2022, this revision has been adopted only in Egypt. Many North African countries are yet to adopt a first draft of the formalized guidance. This analysis revealed that, although many of these countries reference the WHO guidelines, hesitation remains in terms of sourcing comparator products outside the US or European countries. This likely translates to slow regional development and cooperation of functioning, sustainable biosimilars markets. Future studies will be necessary to evaluate the continued development of guidance within these countries and changes in comparator sourcing norms as more time is allowed for their policies to mature and adapt to new standards.

This project convened a series of meetings and workshops to prioritize listening to multi-sector stakeholders from local government, advocacy, and industry in US cities where autonomous vehicles are operating. The objective was to listen and learn from all stakeholders, raise issues surrounding accessibility and equity, and to solicit responses. Key findings from the workshops include a consensus across the three sectors on the need for good channels of multi-stakeholder communication, and voices across all sectors agreed on the importance of disability access and serving diverse populations. Many parties, representing voices from all sectors, recognized that federal regulatory activities appear to be moving too slowly. Preventing any roadway incidents is a priority for many stakeholders, and some suggest a playbook for handling day-to-day roadway issues and common standards for first-responder interactions. Disability access is a high priority across all sectors, and there many see nearer term to accommodations for blind, hearing-impaired riders, but the timeline for providing service to people with non-folding wheelchairs is less clear. There is also ongoing debate surrounding the limits of regulatory purview, the role for cities, and how to actualize equitable expansion into rural areas. There is more work to do to advance a multi-sector dialogue around the role for local governments and community-based organizations in shepherding a safe, equitable and sustainable expansion of autonomous vehicles.

The vast majority of all global species have circadian rhythm cycles that allow them to adapt to natural environments. These regular rhythms are regulated by core clock genes and recent studies have also implicated roles for microRNAs in this regulation. Oviposition is an important circadian behavior in the reproductive cycle of insect vectors of diseases, and little is known about the rhythm or its regulation in mosquitoes. Aedes albopictus is a diurnal mosquito that transmits arboviruses and is the major cause of outbreaks of dengue fever in China. We analyzed the oviposition rhythm patterns of A. albopictus under different light/dark conditions and show that the mosquitoes have an oviposition peak between zeitgeber time 9 (ZT 9) and ZT 12. Furthermore, the antagomir-mediated knockdown of expression of the microRNA miR-2940-1 affected the oviposition rhythm of A. albopictus. These data support the conclusion that miR-2940-1 is involved in the regulation of oviposition rhythm in A. albopictus and provide a foundation for using oviposition rhythms as a new target for vector mosquito control.

Advanced air mobility (AAM) is a broad concept that enables consumers access to air mobility, goods delivery, and emergency services through an integrated and connected multimodal transportation network. AAM can provide short-range urban, suburban, and rural flights of about 50-miles and mid-range regional flights up to a several hundred miles. State law delegates responsibility for oversight in aviation primarily to the California Department of Transportation (Caltrans). This white paper presents an overview of the state of the market, such as the aircraft under development and forecast market growth and discusses factors that could facilitate the development of AAM or pose risks to its deployment or to the public, including the safety and the regulatory environment, airspace and air traffic management, security, environmental impacts, weather, infrastructure and multimodal integration, workforce and economic development, social equity, and community engagement and social acceptance. It concludes by recommending actions that Caltrans and other state agencies can take to facilitate the development of AAM.

BackgroundElectronic health records (EHRs) are a cost-effective approach to provide the necessary foundations for clinical trial research. The ability to use EHRs in real-world clinical settings allows for pragmatic approaches to intervention studies with the emerging adult HIV population within these settings; however, the regulatory components related to the use of EHR data in multisite clinical trials poses unique challenges that researchers may find themselves unprepared to address, which may result in delays in study implementation and adversely impact study timelines, and risk noncompliance with established guidance.ObjectiveAs part of the larger Adolescent Trials Network (ATN) for HIV/AIDS Interventions Protocol 162b (ATN 162b) study that evaluated clinical-level outcomes of an intervention including HIV treatment and pre-exposure prophylaxis services to improve retention within the emerging adult HIV population, the objective of this study is to highlight the regulatory process and challenges in the implementation of a multisite pragmatic trial using EHRs to assist future researchers conducting similar studies in navigating the often time-consuming regulatory process and ensure compliance with adherence to study timelines and compliance with institutional and sponsor guidelines.MethodsEight sites were engaged in research activities, with 4 sites selected from participant recruitment venues as part of the ATN, who participated in the intervention and data extraction activities, and an additional 4 sites were engaged in data management and analysis. The ATN 162b protocol team worked with site personnel to establish the necessary regulatory infrastructure to collect EHR data to evaluate retention in care and viral suppression, as well as para-data on the intervention component to assess the feasibility and acceptability of the mobile health intervention. Methods to develop this infrastructure included site-specific training activities and the development of both institutional reliance and data use agreements.ResultsDue to variations in site-specific activities, and the associated regulatory implications, the study team used a phased approach with the data extraction sites as phase 1 and intervention sites as phase 2. This phased approach was intended to address the unique regulatory needs of all participating sites to ensure that all sites were properly onboarded and all regulatory components were in place. Across all sites, the regulatory process spanned 6 months for the 4 data extraction and intervention sites, and up to 10 months for the data management and analysis sites.ConclusionsThe process for engaging in multisite clinical trial studies using EHR data is a multistep, collaborative effort that requires proper advanced planning from the proposal stage to adequately implement the necessary training and infrastructure. Planning, training, and understanding the various regulatory aspects, including the necessity of data use agreements, reliance agreements, external institutional review board review, and engagement with clinical sites, are foremost considerations to ensure successful implementation and adherence to pragmatic trial timelines and outcomes.

In the article, the authors made a thorough description of administrative and legal regulation in the field of land relations. They characterized the concepts of «regulation», «legal regulation» and «land relations». It is substantiated that land relations are one of the largest massifs of public relations regulated by legal norms, in which the absolute majority of both private and public legal entities are involved. But due to the diversity of such subjects and the differences in their legal status, the legal regulation of land relations uses methods characteristic of both civil and administrative law. In addition, within the limits of land law, the existence of its own method of legal regulation is emphasized. It was determined that «legal regulation» can be considered an institution of a general type, which includes specific characteristics that give rise to administrative and legal regulation. The formulated author's definition of «administrative-legal regulation» as a type of sectoral legal regulation, which is based on the direct effect of the norms of administrative law and is an administrative-legal instrument that affects social relations arising in the field of public administration. taking into account the peculiarities of the legislative definition of the concept of «land relations», for the purposes of scientific research it is more correct to use the term «administrative-legal regulation in the field of land relations» as opposed to the term «administrative-legal regulation of land relations». In our opinion, the term «sphere of land relations» should be understood as a set of relations, which, in addition to land relations, include relations arising in connection with the exercise of power by public administration bodies in relation to land management. The objects of these relations are land, land plots, rights to them, as well as goods and objects derived from them. «Administrative and legal regulation in the field of land legal relations» should be understood as a type of sectoral legal regulation, which is based on the direct effect of the norms of administrative, civil and land law and is a legal instrument that affects public land legal relations arising in the field of public land management affairs. [ABSTRACT FROM AUTHOR]

It is indicated that the armed aggression of the Russian Federation against Ukraine, which has been going on for the third year, and the progress of European integration processes taking place in our country, require overcoming challenges in the field of higher legal education. One of the important such challenges is the increase in demand from employers for qualified graduates of higher educational institutions who have modern theoretical and practical training in the fields of tax, administrative, contractual, economic and corporate law. At the same time, there is a high demand among employers for specialists who specialize in the field of corporate relations for legal support of the business activities of international corporations working in the agricultural and other sectors of the Ukrainian economy; participation in international and national arbitration and commercial courts in the consideration of corporate disputes in the interests of companies that do not fulfill their obligations in favor of counterparties that maintain relations with the aggressor state or sanctioned persons; judicial protection of corporate rights of foreign and domestic investors; protection in international arbitrations of the interests of Ukrainian business companies that supply material property for the Armed Forces of Ukraine in case of violation of their obligations to them by foreign companies; participation in legal proceedings regarding the recovery of funds and other assets from sanctioned persons in favor of Ukraine or its business entities, etc. The article examines ways of reforming higher legal education in the conditions of armed aggression of russian federation against Ukraine and its European integration into the European Union. The current requirements of employers for law graduates of higher educational institutions are analyzed. The proposed vectors of reforming the educational process, in particular, from the corporate law course, through the introduction of innovative educational programs that meet international world standards, including EU requirements in the field of higher legal education. The need to develop and use interdisciplinary educational programs for the training of lawyers is substantiated. It is recommended that a separate section in these programs provide for the teaching of a corporate law course. Suggested topics from this course include, in particular, corporate law under martial law; adaptation of Ukrainian corporate legislation to the legislation of the European Union - status and prospects; the accession of Ukraine to the European Union as a factor in its victory over russian aggressor country and other topics. A comparative analysis of EU directives and regulations and Ukrainian legislation regulating corporate relations was made. [ABSTRACT FROM AUTHOR]

Background: Regulatory processes can be stressful, anxiety provoking, and complicated for the health professional involved, the institutions they work for, and for the regulators. Methods: This paper uses a case study to describe a systems approach to comprehensively identify the agents (ie: the complainant, the health professional concerned, the regulator dedicated to the case, the institution, the healthcare profession, the public, and the regulatory authority) and 6 ethical issues that emerge during the regulatory process: potential to cause harm, not in the best interest of a person, affects autonomy, unjust, not truthful, and loss of trust. Results: A systems approach lends to a mental model in which there are dynamic interactions across these elements accompanied by positive and negative feedback loops that maintain overall stability of the whole system. Conclusions: The process can be further refined and kinder to those concerned by developing a sensitive approach to improve assessment of risks, using feedback to improve the regulatory process, adapting transparent procedures, not causing undue delays to the process, embedding regulatory activities in a patient safety system, minimizing individual blame, using non-legalistic, non-threatening and respectful communications, and directing the different actors to a support network for guidance and advice. [ABSTRACT FROM AUTHOR]

The World Health Organization has released its first comprehensive Guidance document on health practitioner regulation, addressing a critical gap in global health policy. This Commentary provides an overview of the Guidance, which aims to support countries in strengthening their regulatory systems for health practitioners. The Guidance, developed through a rigorous process involving a literature review and expert consultation, covers a broad range of health practitioners and focuses on optimizing their utilization to meet population health needs. Key highlights include the description of the global regulatory landscape, identification of regulatory challenges in all societies, and policy considerations to realize dynamic, effective, and agile regulation. The COVID-19 pandemic is cited as an important example of a catalyst for regulatory reforms that enhanced workforce availability and access. This paper, co-authored by members of the World Health Organization Technical Expert Group, emphasizes the importance of aligning regulatory systems with broader health workforce and system priorities, adopting a risk-based approach, and addressing implementation gaps. It encourages policymakers, regulators, and researchers to use the Guidance to assess and update their regulatory systems and to generate more robust evidence on the impact of health practitioner regulation on health outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To identify risk and protective factors associated with physician performance in practice; to use this information to create a risk assessment scale; and, to test use of the risk assessment scale with a new population of assessed physicians. Design: Physician assessments that were completed by community-based physicians between March 2016 and February 2022 (n=2708) were gathered to determine what professional characteristics and practice context factors were associated with poor peer practice assessment (PPA). The predictive capacity of the resulting model was then tested against a new sample of physician assessments completed between March 2022 and February 2023 (n=320). Results: N=2401 physicians were eligible for inclusion in a logistic regression analysis, which resulted in an empirical model containing 11 variables that was able to account for 21.6% of the variance in the likelihood of receiving a poor PPA generated by the College of Physicians and Surgeons of British Columbia. The resulting model, when tested against 320 new cases, was able to predict good versus poor PPA performance with a sensitivity of 0.79 and specificity of 0.75. Not having undertaken peer review (OR=1.47) created a risk like that arising from a full decade passing since completion of medical school (OR=1.50). Conclusion: In addition to being the largest known study of its type, this work builds on similar studies by demonstrating the capacity to use regulator-mandated peer review to empirically identify physicians who are at risk of substandard performance using factors that are safe from claims of violating Human Rights Codes; that emphasize modifiable aspects of practice; and that can be readily updated to account for change over time. [ABSTRACT FROM AUTHOR]

The production of cellulolytic enzymes in response to inducible carbon sources is mainly regulated at the transcriptional level in filamentous fungi. We have identified a cellobiose-response regulator (ClbR) controlling the expression of cellulolytic enzyme-encoding genes in Aspergillus aculeatus. However, the engineering potential of combining the deletion of transcriptional repressors with the overexpression of transcriptional activators to enhance enzyme production has not been analyzed. Here, we investigated the effect of the deletion of the transcriptional repressor creA and the overexpression of the transcriptional activator clbR in enzyme production in A. aculeatus. Here, we verified that a combination of creA deletion and clbR overexpression (Δc&OE) improved cellulase, β-1,4-xylanase, and β-glucosidase production. Cellulase and β-1,4-xylanase production increased 3.4- and 8.0-fold in Δc&OE compared with the host strain (MR12) at 96-h incubation, respectively. β-Glucosidase production in Δ creA and Δc&OE increased approximately 5.0-fold compared with that in MR12 at 240-h incubation. Transcriptional analysis revealed that the increase in enzyme production was due to increased expression of cellobiohydrolase, endo-β-1,4-glucanase, β-1,4-xylanase, and β-glucosidase 1 (bgl1). Interestingly, bgl1 expression in Δ creA increased in a dose-dependent manner in response to glucose. Thus, combinational manipulation of transcription factors improved cellulase, xylanase, and β-glucosidase production in A. aculeatus. [ABSTRACT FROM AUTHOR]

Kiwifruit growth and development are severely affected by various biotic and abiotic stresses, especially cold stress and the bacterial disease caused by Pseudomonas syringae pv. actinidiae (Psa). Metallothioneins (MTs) are a group of cysteine-rich proteins that play crucial roles in stress response, metal detoxification, and homeostasis in plants. However, the protective role of these MTs in kiwifruit remains to be elucidated. In the present study, four AcMT genes were identified in the Hongyang kiwifruit genome, namely, two Type 2 isoforms (AcMT2 and AcMT2a) and two Type 3 isoforms (AcMT3a and AcMT3b) located separately on four different chromosomes. The hormones and stress response cis-elements within the promoter regions of these AcMTs were characterized. It was revealed that the four AcMT genes exhibited different expression patterns in different tissues: AcMT2 and AcMT2a were expressed at much higher levels in the fruit, male flower, female flower, root, and bark, while AcMT3a was expressed mainly in the fruit and AcMT3b was expressed highly in the bark. The expression patterns of these AcMT genes after exposure to Psa infection and different phytohormones, including gibberellic acid A3(GA3), ethylene (ET), and abscisic acid (ABA), were evaluated. It was revealed that in response to Psa infection, the main AcMTs in each tissue (those with expression levels higher compared to the other MTs in that tissue) were downregulated during the early stage in kiwifruits, followed by a recovery phase. In addition, most AcMTs were downregulated after exposure to ET and GA3, while type 2 AcMTs (AcMT2 and AcMT2a) were upregulated after treatment with ABA. The overexpression of AcMTs in Escherichia coli presented a higher tolerance to H2O2, heavy metals, low temperature, and high temperature. Collectively, these findings demonstrated the protective roles of AcMTs in terms of stress resistance conferred through plant hormone-related signal pathways. [ABSTRACT FROM AUTHOR]

The article "Big Tech Platforms: What Are the Limits to 'Big Brother' Surveillance and Influence?" by Annabelle Gawer discusses the unprecedented economic power and influence of Big Tech platforms like Google, Amazon, Apple, and Facebook. These platforms dominate various sectors, such as digital advertising, e-commerce, and social media, raising concerns about privacy, data exploitation, and manipulation of user behavior. The article highlights the need for both public regulation and self-regulation to address these issues and prevent exploitation, emphasizing the importance of users' sovereignty in decision-making within platform ecosystems. [Extracted from the article]

Does corruption ease the burden of regulation? We test this question using survey data on business managers' experience in dealing with regulation and corruption. We find that there is substantial within-country variation in the burden of regulation and that corruption is associated with worse regulatory outcomes across a range of indicators at the country, national, and firm level. These findings suggest that corruption is associated with an increase in the burden of regulation, and imposes large costs on businesses. While corruption is associated with an increased burden of regulation, this does not seem to happen through an increase in how much time senior managers must devote to regulation, suggesting that the cost of corruption-induced regulation manifests in the form of additional staff costs or professional fees. [ABSTRACT FROM AUTHOR]

Neurotechnology and Artificial Intelligence (AI) have developed rapidly in recent years with an increasing number of applications and AI-enabled devices that are about to enter the market. While promising to substantially improve quality of life across various severe medical conditions, there are also concerns that the convergence of these technologies, e.g., in the form of intelligent neuroprostheses, may have undesirable consequences and compromise cognitive liberty, mental integrity, or mental privacy. Therefore, various international organizations, such as the Organization for Economic Cooperation and Development (OECD) or United Nations Educational, Scientific and Cultural Organization (UNESCO), have formed initiatives to tackle such questions and develop recommendations that mitigate risks while fostering innovation. In this context, a first international conference on the ethics and regulation of intelligent neuroprostheses was held in Berlin, Germany, in autumn 2023. The conference gathered leading experts in neuroscience, engineering, ethics, law, philosophy as well as representatives of industry, policy making and the media. Here, we summarize the highlights of the conference, underline the areas in which a broad consensus was found among participants, and provide an outlook on future challenges in development, deployment, and regulation of intelligent neuroprostheses. [ABSTRACT FROM AUTHOR]

Summary Reactive oxygen species (ROS) are among the most important signaling molecules, playing a significant role in plant growth, development, and responses to various environmental stresses. Respiratory burst oxidase homologs (RBOHs) are key enzymes in ROS production. Plants tightly regulate the activation and deactivation of RBOHs through various post‐translational modifications (PTMs), including phosphorylation, ubiquitination, S‐nitrosylation, and persulfidation. These PTMs fine‐tune ROS production, ensuring normal plant growth and development while facilitating rapid responses to abiotic and biotic stresses. This review discusses the effects of different PTMs on RBOH function and their biological relevance. Additionally, we examine the evolutionary conservation of PTM sites and emphasize the complex interplay between multiple PTMs regulating RBOHs. [ABSTRACT FROM AUTHOR]

Background: Health and social care employees may be involved in professional regulatory proceedings because their alleged behaviour raises health or conduct concerns. Employees, patients or service users may also be involved in a regulatory tribunal as witnesses. This study is about the role of employers in supporting them in this process. Methods: Taking an organisational support perspective, we interviewed 25 senior employees in health and social care organisations in the UK who are responsible for managing the employer's role in the proceedings. Template analysis was used to analyse the transcripts. Results: Support for patients was limited to that offered during an employer's complaints process, and only one employer gave some support during the regulatory process if the patient or service user initiated regulatory proceedings. Support for employees in tribunals was little different to that offered during an initial investigation by the employer. However, where additional support for being involved in a regulatory tribunal was offered to employees, it most often came from the senior employees' own experience of the stressfulness of being a witness in these proceedings. Employers were not aware of training resources that would better support their employees to engage with professional regulatory proceedings. Conclusions: Employers offer limited support to employees who are involved in professional regulatory proceedings, and the support offered may depend more on senior employee's individual experience of involvement in regulatory proceedings to exercise this discretion. Patients, service users and other public witnesses receive almost no support from health and social care employers during professional regulatory proceedings. [ABSTRACT FROM AUTHOR]

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Introduction: Plasmodium falciparum is the most damaging malaria pathogen and brings a heavy burden to global health. Host switching and morphological changes in P. falciparum are dependent on an effective gene expression regulatory system. C5 methylation of cytosines is a common RNA modification in eukaryotes, and the NSUN family are essential m5C modification executors. Currently, little is known about this family in Plasmodium spp. In this study, we focus on exploring the function of PfNSUN1 protein. Methods: An efficient CRISPR/Cas9 gene editing technique was applied to construct the PfNSUN1 knockdown strain. The knockdown efficiency was confirmed by growth curves and western blot experiments. The knockdown transcriptome data was acquired to find differentially expressed genes, and target genes of PfNSUN1 protein were identified by RNA immunoprecipitation and high-throughput sequencing experiments. Results: The efficiency of PfNSUN1 protein down-regulated was about 34%. RNA-seq data revealed that differentially expressed genes were mainly downregulated. And there were 224, 278, 556 genes that were down-regulated with more than 2-fold changes and p-adj<0.05 at ring, trophozoite and schizont stages, respectively. PfNSUN1 protein was significantly enriched on 154 target genes, including 28S ribosomal RNA and pfap2-g5 transcription factor. Discussion: PfNSUN1 is a crucial RNA post-transcriptional modification protein in P. falciparum. It plays a pivotal role in regulating gene expression and parasite growth by targeting 28S ribosomal RNA and pfap2-g5 transcription factor. [ABSTRACT FROM AUTHOR]

Following an outbreak of Cronobacter sakazakii infection in infant formula, the US Food and Drug Administration commissioned a series of reports and then undertook a major reorganization of its food program. This article describes the changes that went into effect on 1 October 2024, why those changes are likely to improve the new Human Foods Program, and additional work that must be undertaken to enhance the agency's impact upon public health. [ABSTRACT FROM AUTHOR]

This study addresses the critical need for innovation in the healthcare sector, particularly in Japan's functional food industry, amid rising chronic diseases and healthcare costs. It explores the complex relationship between regulatory design and corporate behaviour, focusing on how companies' compliance strategies influence their research and development (R&D) investments. A mixed-method approach was used, analysing data from 15 major dietary supplement companies and 74 products under Japan's Foods with Function Claims (FFCs) regulation. The study reveals a correlation between companies' engagement in the FFCs system and their preference for conducting in-house clinical trials, indicative of higher R&D investments (R = 0.66, p = 0.007), and that between the latter variable and average product sales, which is a measure of returns on regulatory compliance (R = 0.66, p = 0.008). Companies actively complying with FFCs regulations tend to conduct R&D and accumulate knowledge in-house, to innovate and differentiate their products, gaining competitive advantages. The study also highlights the role of a company's size, market presence, and industry origins in shaping regulatory strategies, with firms from other industries using FFCs regulations to explore new business opportunities. The research underscores the importance of flexible regulatory frameworks that encourage R&D investment, leading to innovation and competitive advantages in the healthcare sector. [ABSTRACT FROM AUTHOR]

Many nations have food contact material (FCM) legislation purporting to protect citizens from hazardous chemicals, often specifically by regulating genotoxic carcinogens. Despite such regulations, cancers that are associated with harmful chemical exposures are highly prevalent, especially breast cancer. Using the novel Key Characteristics of Toxicants framework, Kay et al. found 921 substances that are potential mammary carcinogens. By comparing Kay et al.'s chemicals list with our own Database on migrating and extractable food contact chemicals (FCCmigex), we found that 189 (21%) of the potential mammary carcinogens have been measured in FCMs. When limiting these results to migration studies published in 2020-2022, 76 potential mammary carcinogens have been detected to migrate from FCMs sold in markets across the globe, under realistic conditions of use. This implies that chronic exposure of the entire population to potential mammary carcinogens from FCMs is the norm and highlights an important, but currently underappreciated opportunity for prevention. Reducing population-wide exposure to potential mammary carcinogens can be achieved by science-based policy amendments addressing the assessment and management of food contact chemicals. [ABSTRACT FROM AUTHOR]

Background: The Jun proto-oncogene (JUN), also referred to as C-JUN, is an integral component of the JNK signaling pathway, which is crucial for the formation and differentiation of spermatogonial stem cells (SSCs). Investigations into the transcriptional regulation of chicken JUN can offer a molecular foundation for elucidating its mechanistic role in SSCs. Methods: In this study, we successfully cloned a 2000 bp upstream sequence of the JUN transcription start site and constructed a series of pGL3 recombinant vectors containing JUN promoters of varying lengths. Results: We verified the promoter activity of the 2000 bp upstream sequence by assessing the fluorescence intensity of DF-1 and identified the promoter activities of different regions via dual-luciferase assays. The transcription of JUN and its promoter region spanning −700 to 0 bp was modulated by an activator of the JNK signaling pathway. Bioinformatics analysis revealed that this −700 to 0 bp region was highly conserved among avian species and predicted the presence of binding sites for Wilms tumor 1 (WT1) and CCAAT/enhancer binding protein alpha (CEBPA). The JNK signaling pathway activator was found to upregulate the expression of these transcription factors in DF-1 cells. Through the deletion of binding sites and the overexpression of WT1 and CEBPA, we demonstrated that WT1 inhibited the transcription of JUN, while CEBPA promoted it. Conclusions: In conclusion, the −700 to 0 bp region is the key region of the JUN promoter, with WT1 inhibiting JUN transcription. The results of the study not only provide ideas for exploring the regulatory mechanism of JUN in chicken SSCs, but also lay an important foundation for the study of avian SSCs. [ABSTRACT FROM AUTHOR]

Public policy addressing biodiversity loss is most likely to be effective when it is informed by appropriate evidence and considers potential unintended consequences. We evaluate key evidence relating to the Hunting Trophies (Import Prohibition) Bill that was discussed in the UK Parliament between 2022 and 2024. We characterize the UK's role in international hunting trophy trade by analyzing CITES (Convention on International Trade in Endangered Species of Wild Fauna and Flora) trade data for 2000–2021 and 2015–2021. For CITES‐listed species imported to/exported from the UK as hunting trophies in these periods we use data from the International Union for Conservation of Nature (IUCN) Red List of Threatened Species to determine whether hunting designated as "trophy hunting" is (i) likely a major threat contributing to species being of elevated conservation concern, (ii) likely or possibly causing localized declines, or (iii) not a threat. We then use the Red List to determine whether such hunting provides, or potentially provides, benefits for species and/or people. Finally, we evaluate the UK Government's impact assessment of the bill. In 2000–2021 an estimated 3494 hunting trophies from 73 CITES‐listed species and subspecies were exported to the UK involving an estimated 2549 whole organism equivalents (WOEs), that is, individual animals. Imports involved 158.86 ± 66.53 (mean ± SD) trophies/year (115.83 ± 32.27 WOEs/year). In 2015–2021, 79% of imports were from countries where populations of the hunted species are stable, increasing, or abundant. Legal hunting for trophies is not a major threat to any of the species or subspecies imported to the UK, but likely or possibly represents a local threat to some populations of eight species. This hunting does, or could potentially, benefit 20 species and subspecies, and people. Among other concerns, the impact assessment failed to adequately consider the costs and benefits to local communities in countries where such hunting occurs. Informed by these analyses we discuss alternative regulatory options. [ABSTRACT FROM AUTHOR]

Recommender Systems (RecSys) have been around since the early days of the Internet, helping users navigate the vast ocean of information and the increasingly available options that have been available for us ever since. The range of tasks for which one could use a RecSys is expanding as the technical capabilities grow, with the disruption of Machine Learning representing a tipping point in this domain, as in many others. However, the increase of the technical capabilities of AI-powered RecSys did not come with a thorough consideration of their ethical implications and, despite being a well-established technical domain, the potential impacts of RecSys on their users are still under-assessed. This paper aims at filling this gap in regards to one of the main impacts of RecSys: personal autonomy. We first describe how technology can affect human values and a suitable methodology to identify these effects and mitigate potential harms: Value Sensitive Design (VSD). We use VSD to carry out a conceptual investigation of personal autonomy in the context of a generic RecSys and draw on a nuanced account of procedural autonomy to focus on two components: competence and authenticity. We provide the results of our inquiry as a value hierarchy and apply it to the design of a speculative RecSys as an example. [ABSTRACT FROM AUTHOR]

[Purpose] During the post-liberalization era, the Indian legal system introduced multiple laws with the objective of safeguarding the interests of Indian consumers and fostering equitable competition within the telecommunications sector. Notably, the Indian legal system has demonstrated a significant commitment to the resolution of telecommunications-related disputes, exemplified by the enactment of the Telecom Regulatory Authority of India (TRAI) Act in 1997 and the Competition Act in 2002. Both legislative measures were designed to advance the cause of fair competition in the telecommunications industry. The primary purpose of this article is to conduct an examination of whether the objectives set forth by these two Acts have been effectively realized over the past decade (2012-2021). Additionally, this article will undertake a comparative analysis of these Acts in relation to legal frameworks in other countries beyond India. [Methodology] The foundational methodology employed in this research centers on the analysis of cases adjudicated by both the Telecom Regulatory Authority and the Competition Regulatory Authority in India, particularly in instances involving disputes within the telecommunications sector. This article offers a concise data analysis concerning the evolution of the Indian telecommunications market over the past decade (2012-2021). The primary aim is to undertake a critical evaluation of the effectiveness of the Acts in place for the preservation of fair competition within this industry. [Findings] Based on the legal analysis, this article argues that there is an unresolved territorial dispute between the Telecom Regulatory Authority of India (TRAI) Under section 3 of the Telecom Regulatory Authority of India Act, 1997, the Indian government established the regulatory agency to oversees the telecommunications industry in India and the Competition Act, 2002 establishes the Competition Commission of India being primary national competition regulator in India. It is an official department of the Ministry of Corporate Affairs tasked with upholding the Competition. The findings also suggest that the Government of India should overhaul its institutional framework in order to insert the "collective dominance" concept in the Competition Act. This concept/amendment was about to be passed in the India Congress by the United Progressive Alliance (UPA) Government in 2014. However, it failed due to dissolution of the Lok Sabha, the lower house of India's bicameral Parliament. Consequently, numerous disputes and concerns remained unresolved. Lastly, Reliance JIO Infocomm Limited is a Public Company that was established on February 15, 2007, is categorized as a Non-Government Company, and is registered with the Registrar of Companies in Mumbai, India. It applied a "zero pricing" strategy which created market distortion which reduced most of the rivals from the telecom market. This kind of strategy was previously ordered void in the NSE1 case but the same was allowed to the JIO on the premises that it was a new entrant and not dominant. The Competition laws mostly address "predatory pricing", however, in the matter of "penetrative pricing" they have remained silent. The "penetrative pricing" is allowed for the promotion, but the benchmark of promotion has not yet been regulated. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new form of cell death that differs from traditional forms of death. It is ferroptosis-dependent lipid peroxidation death. Colorectal cancer(CRC) is the most common tumor in the gastrointestinal tract with a long occultation period and a poor five-year prognosis. Exploring effective systemic treatments for CRC remains a great challenge worldwide. Numerous studies have demonstrated that ferroptosis can participate in the biological malignant process of various tumor, including CRC, so understanding the role and regulatory mechanisms of ferroptosis in CRC plays a crucial role in the treatment of CRC. In this paper, we reviews the mechanisms of ferroptosis in CRC, the associated regulatory factors and their interactions with various immune cells in the immune microenvironment. In addition, targeting ferroptosis has emerged as an encouraging strategy for CRC treatment. Finally, to inform subsequent research and clinical diagnosis and treatment, we review therapeutic approaches to CRC radiotherapy, immunotherapy, and herbal therapy targeting ferroptosis. [ABSTRACT FROM AUTHOR]

We present an empirical analysis of the relationship between trading permits, informal entrepreneurship and unemployment. We exploit a unique regulatory framework of the informal sector in South Africa to estimate the effects of trading permits in the informal sector using individual panel data. To provide a causal effect of these regulations, we apply a difference-in-difference strategy. Trading permits decreased informal entrepreneurship and informal trading by respectively 11.5 per cent and 9.6 per cent for those who were working in the informal sector. We investigate potential indirect effects on formal entrepreneurship, unemployment, and informal wage employment. The adoption of trading permits in the informal sector significantly increases the probability of being unemployed by 4.5 per cent and significantly decreases the probability of being informally employed by 15.5 per cent for those who were in the informal sector. The results suggest that a policy increasing the costs of informality might reduce informality but at the cost of rising unemployment. [ABSTRACT FROM AUTHOR]

The onset of autonomous inland shipping comes with regulatory challenges. First, regulations currently in place do not permit the operation of autonomous ships, mainly due to crewing requirements. Second, autonomous transport modes are deemed to be disruptive technologies that present a particular challenge to public regulators with regard to their potential for unforeseen risks and uncertainties inherent to their implementation. From a public regulator's perspective, it is, therefore, of the utmost importance to identify and regulate the factors currently hindering the introduction of autonomous inland shipping, on the one hand, and the newly emerging issues, on the other hand, to minimise potential risk and uncertainty as much as possible. This paper presents a systematic literature review which was conducted to answer the research question: What factors influence the regulation of autonomous inland shipping? Following the outcome of the literature review, various factors could be identified, and four main categories of factors were established: technological, infrastructure, institutional and socio-economic readiness. The identified factors were subsequently discussed with regard to their significance for the regulatory agenda in light of factors found in the literature on autonomous maritime ships. The findings are of relevance for public regulators and policymakers working in the field of autonomous inland shipping. Moreover, the results presented in this paper might be also of interest for those seeking regulatory innovation regarding autonomous processes in other modes of transport. [ABSTRACT FROM AUTHOR]

Background: The hearing health sector is an example of a health sector that is experiencing a period of rapid innovation driven by digital technologies. These innovations will impact the types of interventions and services available to support the communication of deaf and hard-of-hearing individuals. This study explored the perceptions of informed participants on the topic of innovation and regulation within hearing healthcare in Australia and the United Kingdom (UK). Methods: Participants (N = 29, Australia [n = 16], UK [n = 13]) were purposively sampled and joined one of two online workshops. Participants included adults with hearing loss and family members, hearing health professionals, academics/researchers, representatives of hearing device manufacturers, regulators and policymakers. Workshop data were analysed using reflexive thematic analysis. Results: Participants conceptualised the hearing health sector as a network of organisations and individuals with different roles, knowledge and interests, in a state of flux driven by innovation and regulation. Innovation and regulation were perceived as mechanisms to ensure quality and mitigate risk within a holistic approach to care. Innovations encompassed technological as well as non-technological innovations of potential benefit to consumers. Participants agreed it was essential for innovation and regulation to be congruent with societal values. Critical to ethical congruence was the involvement of consumers throughout both innovation and regulation stages, and the use of innovation and regulation to tackle stigma and reduce health disparities. Participants expressed the desire for accessible and inclusive innovation in the context of fair, transparent and trustworthy commercial practices. Conclusions: This study explored how stakeholders within the hearing health sector understand and make sense of innovation and the role of regulation. Overall, and despite reservations relating to health care professionals' changing roles and responsibilities, innovation and regulation were conceptualised as beneficial when situated in the context of holistic, whole-person, models of care. The results of this study will inform considerations to support the development and implementation of innovations and regulation within the hearing sector and across other health sectors influenced by technological advances. [ABSTRACT FROM AUTHOR]

Phytohormones are signaling substances that control essential elements of growth, development, and reactions to environmental stress. Drought, salt, heat, cold, and floods are a few examples of abiotic factors that have a significant impact on plant development and survival. Complex sensing, signaling, and stress response systems are needed for adaptation and tolerance to such pressures. Abscisic acid (ABA) is a key phytohormone that regulates stress responses. It interacts with the jasmonic acid (JA) and salicylic acid (SA) signaling pathways to direct resources toward reducing the impacts of abiotic stressors rather than fighting against pathogens. Under exposure to nanoparticles, the plant growth hormones also function as molecules that regulate stress and are known to be involved in a variety of signaling cascades. Reactive oxygen species (ROS) are detected in excess while under stress, and nanoparticles can control their formation. Understanding the way these many signaling pathways interact in plants will tremendously help breeders create food crops that can survive in deteriorating environmental circumstances brought on by climate change and that can sustain or even improve crop production. Recent studies have demonstrated that phytohormones, such as the traditional auxins, cytokinins, ethylene, and gibberellins, as well as more recent members like brassinosteroids, jasmonates, and strigolactones, may prove to be significant metabolic engineering targets for creating crop plants that are resistant to abiotic stress. In this review, we address recent developments in current understanding regarding the way various plant hormones regulate plant responses to abiotic stress and highlight instances of hormonal communication between plants during abiotic stress signaling. We also discuss new insights into plant gene and growth regulation mechanisms during stress, phytohormone engineering, nanotechnological crosstalk of phytohormones, and Plant Growth-Promoting Rhizobacteria's Regulatory Powers (PGPR) via the involvement of phytohormones. [ABSTRACT FROM AUTHOR]

Cys is one of the least abundant amino acids in proteins. However, it is often highly conserved and is usually found in important structural and functional regions of proteins. Its unique chemical properties allow it to undergo several post-translational modifications, many of which are mediated by reactive oxygen, nitrogen, sulfur, or carbonyl species. Thus, in addition to their role in catalysis, protein stability, and metal binding, Cys residues are crucial for the redox regulation of metabolism and signal transduction. In this review, we discuss Cys post-translational modifications (PTMs) and their role in plant metabolism and signal transduction. These modifications include the oxidation of the thiol group (S-sulfenylation, S-sulfinylation and S-sulfonylation), the formation of disulfide bridges, S-glutathionylation, persulfidation, S-cyanylation S-nitrosation, S-carbonylation, S-acylation, prenylation, CoAlation, and the formation of thiohemiacetal. For each of these PTMs, we discuss the origin of the modifier, the mechanisms involved in PTM, and their reversibility. Examples of the involvement of Cys PTMs in the modulation of protein structure, function, stability, and localization are presented to highlight their importance in the regulation of plant metabolic and signaling pathways. [ABSTRACT FROM AUTHOR]

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Low back pain (LBP) is largely attributed to intervertebral disc degeneration (IVDD), of which the endplate changes are an important component. However, the alterations in cell fate and properties within the endplates during degeneration remain unknown. Here, we firstly performed the single-cell RNA-sequencing analysis (scRNA-seq) of the cells focusing on degenerative human endplates. By unsupervised clustering of the 8,534 single-cell based on the gene expression, we identified nine distinct cell types. We employed Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, and the single-cell regulatory network inference and clustering (SCENIC) to determine the enriched pathways and transcriptional activities across seven chondrocyte subpopulations. Furthermore, two cell fates of chondrocyte differentiation were found by trajectory analysis, one was enriched in inflammation-related genes, and the other was related to extracellular matrix (ECM). Additionally, the intercellular interactions of macrophages (MA) and chondrocytes, T cells/natural killer cells (T/NK) and chondrocytes were examined by ligand-receptor pairs analysis, showing the important regulative function of FN1 from MA and CD74 from T/NK during endplate degeneration. Overall, our findings provide novel perspectives on the endplate degeneration at the single-cell level and a whole-transcriptome size. [ABSTRACT FROM AUTHOR]

Background: Engineering bacteria with the purpose of optimizing the production of interesting molecules often leads to a decrease in growth due to metabolic burden or toxicity. By delaying the production in time, these negative effects on the growth can be avoided in a process called a two-stage fermentation. Main text: During this two-stage fermentation process, the production stage is only activated once sufficient cell mass is obtained. Besides the possibility of using external triggers, such as chemical molecules or changing fermentation parameters to induce the production stage, there is a renewed interest towards autoinducible systems. These systems, such as quorum sensing, do not require the extra interference with the fermentation broth to start the induction. In this review, we discuss the different possibilities of both external and autoinduction methods to obtain a two-stage fermentation. Additionally, an overview is given of the tuning methods that can be applied to optimize the induction process. Finally, future challenges and prospects of (auto)inducible expression systems are discussed. Conclusion: There are numerous methods to obtain a two-stage fermentation process each with their own advantages and disadvantages. Even though chemically inducible expression systems are well-established, an increasing interest is going towards autoinducible expression systems, such as quorum sensing. Although these newer techniques cannot rely on the decades of characterization and applications as is the case for chemically inducible promoters, their advantages might lead to a shift in future inducible expression systems. [ABSTRACT FROM AUTHOR]

Background: Radiopharmaceuticals have been considered a special group of medicines in Europe since 1989. The use of radiopharmaceuticals that have marketing authorization should always be the first option in clinical use, however due to their special properties the availability of approved radiopharmaceuticals is limited. For this reason, they can be produced on a small scale outside the marketing authorization process. Main body: The in-house radiopharmaceutical preparations represent an important source of these special medicines for routine nuclear medicine practice. However, a lack of harmonization in Member States' regulations leads to extreme differences in the use and availability of radiopharmaceuticals across Europe. The aim of this work is to provide an overview of the different national regulatory frameworks in which Directive 2001/83/UE is adopted on the preparation of radiopharmaceuticals outside the marketing authorization track in Europe. Nine different national regulations have been studied to describe how unlicensed radiopharmaceuticals are prepared. Special attention is paid to reflect the minimum standards that these preparations should meet as well as the educational requirements to be a radiopharmacist in charge of them. Conclusion: The rapid development of new radiopharmaceuticals used in radiometabolic therapy requires a common regulation that allows balance between the use and preparation of licensed and unlicensed radiopharmaceuticals. The absence of a harmonized regulation for the radiopharmaceutical small-scale preparation and the implementation of Good Manufacture Practices, leads to extreme differences in the use, quality assurance and availability of radiopharmaceuticals in Europe. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) demonstrates various opportunities and risks. Our study explores the trade-off of AI technology, including existential risks. We develop a theory and a Bayesian simulation model in order to explore what is at stake. The study reveals four tangible outcomes: (i) regulating existential risks has a boundary solution of either prohibiting the technology or allowing a laissez-faire regulation. (ii) the degree of 'normal' risks follows a trade-off and is dependent on AI-intensity. (iii) we estimate the probability of 'normal' risks to be between 0.002% to 0.006% over a century. (iv) regulating AI requires a balanced and international approach due to the dynamic risks and its global nature. [ABSTRACT FROM AUTHOR]

Due to the fast-changing environments caused by artificial intelligence development, the socio-technical challenge in contemporary educational systems focuses on the need for more regulative measures guiding system stakeholders' behavior. In fulfilling the present legal gap, enacted soft law regulation has been laid out, and a detailed systematic literature review was conducted in the paper presented. The specific methodological approach was selected to deal with two crucial research tasks: to reveal and recommend fundamental governing mechanisms regarding the use and application of generative artificial intelligence; more precisely, large language models in educational systems. Three systematically guided layers of quantitative and qualitative content analysis of central policy, legislation, and regulatory mechanisms in governing AI in education were extracted from the 142 Scopus Database and Web of Science research papers analyzed and presented. These research findings benefit policymakers, regulatory and legislative bodies, and agencies in constructing governing frames for using and applying generative artificial intelligence in education. [ABSTRACT FROM AUTHOR]

With increasing interest in the emotional responses to music, some studies are specifically looking into music's regulatory function on emotion, known as "music emotion regulation (MER)". The purpose of this study was to examine the concepts on the regulatory impact of music on emotion using a scoping review procedure. Through an electronic database and manual searches based on the guidelines suggested by the JBI Manual for Evidence Synthesis, a total of 47 studies were identified and included for analysis. The results showed that there were some definitional challenges in each component of music emotion regulation. Most studies treated music as a single variable without exploring the regulatory mechanism of the intra-musical elements that constitute music. When examining the regulatory impact of music on emotion, emotion was inclusive of other terms ranging from feeling to mood. Most of the MER studies employed the terms used in the emotion regulation strategies; however, there were some regulatory processes that pertained solely to music's cathartic effect. Overall, the results showed that music emotion regulation (MER) was not clearly distinguished from music emotion (ME) studies. Future research should allocate more attention to the theoretical mechanism behind music's intrinsic regulatory effect in emotion regulation (MER) studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Diapause is a state in which insects respond to environmental changes, leading to developmental stagnation, which is crucial in the life history of insects. miRNA regulates the expression of genes after transcription and participates in the regulation of important biological processes of insect growth and development. In this study, we screened differentially expressed miRNAs (DEMs) in non-diapause/diapause and diapause/non-diapause comparison groups of Ostrinia furnacalis and predicted their target genes. The expression patterns of key target genes Kr-h, JHE, JHEH, FOXO, Cry, and Per in diapause-related metabolic pathways at different stages of diapause were opposite to those of miRNAs, suggesting their regulatory roles in the diapause process. This study improves the scientific understanding of diapause in O. furnacalis; the learning can be applied to other insects. microRNAs (miRNAs) function as vital regulators of diapause in insects through their ability to post-transcriptionally suppress target gene expression. In this study, the miRNA of Ostrinia furnacalis, an economically important global crop pest species, was characterized. For the included analyses, 9 small RNA libraries were constructed using O. furnacalis larvae in different diapause states (non-diapause, ND; diapause, D; diapause-termination, DT). The results identified 583 total miRNAs, of which 256 had previously been identified, whereas 327 were novel. Furthermore, comparison analysis revealed that 119 and 27 miRNAs were differentially expressed in the D vs. ND and DT vs. D, respectively. Moreover, the expression patterns of their miRNAs were also analyzed. GO and KEGG analysis of the target genes of differentially expressed miRNAs highlighted the importance of these miRNAs as diapause regulators in O. furnacalis, especially through metabolic processes, endocrine processes, 20-hydroxyecdysone, and circadian clock signaling pathways. In summary, this study highlighted the involvement of specific miRNAs in the control of diapause in O. furnacalis. To the best of our knowledge, this is the first study to identify miRNA expression patterns in O. furnacalis, thereby providing reference and novel evidence enhancing our current understanding of how small RNAs influence insect diapause. [ABSTRACT FROM AUTHOR]

Summary: Vascular bundles transport water and photosynthate to all organs, and increased bundle number contributes to crop lodging resistance. However, the regulation of vascular bundle formation is poorly understood in the Arabidopsis stem.We report a novel semi‐dominant mutant with high vascular activity, hva‐d, showing increased vascular bundle number and enhanced cambium proliferation in the stem. The activation of a C2H2 zinc finger transcription factor, AT5G27880/HVA, is responsible for the hva‐d phenotype. Genetic, biochemical, and fluorescent microscopic analyses were used to dissect the functions of HVA.HVA functions as a repressor and interacts with TOPLESS via the conserved Ethylene‐responsive element binding factor‐associated Amphiphilic Repression motif. In contrast to the HVA activation line, knockout of HVA function with a CRISPR‐Cas9 approach or expression of HVA fused with an activation domain VP16 (HVA‐VP16) resulted in fewer vascular bundles. Further, HVA directly regulates the expression of the auxin transport efflux facilitator PIN1, as a result affecting auxin accumulation. Genetics analysis demonstrated that PIN1 is epistatic to HVA in controlling bundle number.This research identifies HVA as a positive regulator of vascular initiation through negatively modulating auxin transport and sheds new light on the mechanism of bundle formation in the stem. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The global food animal industry faces a growing concern regarding antimicrobial resistance (AMR), primarily driven by the use of antimicrobials (AM) for the treatment, control, and prevention of diseases. Addressing this challenge requires promoting responsible antimicrobial use (AMU) practices. In 2019, the province of Québec, Canada, took a significant step by implementing a regulation that limits the use of AM of very high importance for human medicine (category I AM as defined by Health Canada) in the food animal industry. However, the implementation of such regulation can significantly influence behavioral shifts among producers, contributing to the wider effort against AMR. Therefore, the objective of this observational study was to describe the perceived changes in dairy producers' knowledge and on-farm practices following the implementation of this regulation, using a cohort design. Data collection involved administering questionnaires to 87 dairy producers from 3 regions of the province of Québec (Estrie, Montérégie, Centre-Du-Québec) before (2017–2018) and after (2020–2021) the implementation of the regulation. The questionnaires explored the descriptive characteristics of farms, the knowledge of producers about the categorization of AM, the on-farm treatment practices, and the perceived effects of the regulation. Statistical analysis included t -tests and McNemar tests to compare the paired data obtained using the 2 questionnaires. The results indicated an increase in the knowledge score (the number of AM correctly categorized by the producers by their importance for human medicine) after the implementation of the regulation, suggesting an improved understanding of the categorization of AM based on their importance for human medicine. Trends in AMU practices for treating clinical mastitis and reproductive diseases suggested that category I AM were less likely to be reported as the primary treatment after the regulation, whereas category II AM were more often reported as primary treatment. Adoption of the selective dry cow therapy method significantly increased, whereas the use of teat sealants remained unchanged. Moreover, producers had divergent perceptions regarding the effect of the regulation on the cure rates and disease frequencies. This disparity emphasizes the need for comprehensive data collection to discern the risks associated with such regulatory shifts. The study acknowledges several limitations, including the potential for recall bias, confirmation bias, and desirability bias. Despite these limitations, this study shows that implementing regulations to encourage responsible AMU drives positive transformations in producers' knowledge and on-farm practices. This underscores the pivotal effect of proactive interventions in combating the escalating threat of AMR within the global food animal industry. [ABSTRACT FROM AUTHOR]

This paper describes the establishment of banking supervision in Italy and its operation between 1926 and 1936, using a narrative approach based on previously classified documents from the Bank of Italy's Historical Archives. This case is particularly interesting from the international perspective, Italy having been the first European country to assign substantial supervision to its central bank, a few years before the 1929 crisis. Notwithstanding insufficient regulation and a light touch concerning the four major mixed banks, we document considerable enforcement of the law, which went beyond the initial provisions, thanks to the rather proactive supervisory approach adopted by the Bank of Italy. [ABSTRACT FROM AUTHOR]

Four topics related to the operation of regulatory systems are considered. These concern the matters of dealing with globally sub‐optimal decisions made by regulators, the problem of specifying boundaries between groups of regulated entities in the application of regulation, dealing with a situation in which there are multiple regulators, and the alignment of regulation across jurisdictional borders. It is argued that current responses to these dilemmas tend to add to levels of inefficiency in the economy, with consequences for growth. Options for resolving them are considered, including new approaches to the design of regulation. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) systems provide acquired heritable protection to bacteria and archaea against selfish DNA elements, such as viruses. These systems must be tightly regulated because they can capture DNA fragments from foreign selfish elements, and also occasionally from self-chromosomes, resulting in autoimmunity. Most known species from the halophilic archaeal genus Haloferax contain type I-B CRISPR-Cas systems, and the strongest hotspot for self-spacer acquisition by H. mediterranei was a locus that contained a putative transposable element, as well as the gene HFX_2341, which was a very frequent target for self-targeting spacers. To test whether this gene is CRISPR-associated, we investigated it using bioinformatics, deletion, over-expression, and comparative transcriptomics. We show that HFX_2341 is a global transcriptional regulator that can repress diverse genes, since its deletion results in significantly higher expression of multiple genes, especially those involved in nutrient transport. When over-expressed, HFX_2341 strongly repressed the transcript production of all cas genes tested, both those involved in spacer acquisition (cas1, 2 and 4) and those required for destroying selfish genetic elements (cas3 and 5–8). Considering that HFX_2341 is highly conserved in haloarchaea, with homologs that are present in species that do not encode the CRISPR-Cas system, we conclude that it is a global regulator that is also involved in cas gene regulation, either directly or indirectly. [ABSTRACT FROM AUTHOR]

In "Robust Financial Networks," F. Hu, D. Mitchell, and S. Tompaidis study networks of financial institutions where only aggregate information on liabilities is available. The authors introduce the robust liability network, that is, the network consistent with the available information that exhibits the worst expected losses. They provide an algorithm to identify the robust liability network and, using aggregate data provided by bank holding companies to the Federal Reserve in form FR Y-9C, determine robust liability networks for U.S. banks under various network configurations. They show that the robust liability network is sparse, with links between institutions that hold highly correlated portfolios. They illustrate the methodology in two applications. (1) They look at how robust liability networks changed around the onset of the COVID-19 pandemic. (2) They evaluate the impact of a potential regulation that limits risk-taking based on each institution's conditional value-at-risk. Their results can be used by regulators to monitor systemic risk in financial networks. We study networks of financial institutions where only aggregate information on liabilities is available. We introduce the robust liability network, that is, the network with the worst expected losses among all networks with the same aggregate liabilities and assets. We provide an algorithm to identify the robust liability network and, using aggregate data provided by bank holding companies to the Federal Reserve in form FR Y-9C, determine robust liability networks for U.S. banks under various network configurations. We find that the robust liability network is sparse, with links between institutions that hold highly correlated portfolios. We illustrate the potential of our approach in two ways: We study the evolution of robust liability networks around the onset of the COVID-19 pandemic and evaluate the importance of network structure for financial institutions that are subject to a regulation that limits risk-taking based on each institution's conditional value-at-risk. Supplemental Material: The online appendices and data files are available at https://doi.org/10.1287/opre.2022.0272. [ABSTRACT FROM AUTHOR]